PDA Journal of Pharmaceutical Science and Technology最新文献

{"title":"Proactive Replacement in Aseptic Manufacturing: A Health Index + Weibull/Kaplan--Meier Framework.","authors":"SaiVijay Thattukolla, Sai Vinay Thattukolla","doi":"10.5731/pdajpst.2025-000055.1","DOIUrl":"10.5731/pdajpst.2025-000055.1","url":null,"abstract":"<p><p>Aseptic manufacturing depends on reliable equipment to maintain throughput and protect patients. This study presents a practical, reproducible maintenance engineering method for proactively replacing aging parts before failure; regulatory references are included only as bounded implementation context for execution inside governed (site validated) systems. This study presents a practical, reproducible method for proactively replacing aging parts before failure. The method combines a simple weighted Health Index (HI) that summarizes condition signals such as vibration, temperature, flow, pressure decay, and motor torque with established survival methods (Weibull and Kaplan-Meier) to estimate remaining useful life (RUL). These estimates are converted into clear Green-Yellow-Red maintenance actions and illustrated with a conceptual SAP Plant Maintenance execution workflow for work orders, spare reservation, and traceable recordkeeping under site governance. The workflow is demonstrated on a vial washer, an upstream step that influences vial cleanliness and particulate control prior to depyrogenation, focusing on components including conveyors, pumps, bearings, seals, spray nozzles, and heaters. Using a simulation dataset to illustrate the full end-to-end analytics and decision workflow, Weibull fits with shape factor β in the range of about 1.8 to 2 captured wears out behavior, and Kaplan-Meier pump survival at 24 months was 0.58 (95% CI 0.50 to 0.66). Applying HI together with RUL shifted interventions from unplanned breakdowns to planned stops. Relative to a reactive baseline under the stated assumptions, the scenario results showed 62.5% lower downtime, 84% lower combined maintenance and rejection costs, and 50% fewer batch rejects, with robustness demonstrated through sensitivity tests and 1000 Monte Carlo runs. Overall, the contribution is a reproducible maintenance engineering workflow (HI + survival-based RUL + decision matrix) with a conceptual Computerized Maintenance Management Systems (CMMS)/SAP Plant Maintenance execution mapping for traceable work order initiation when implemented under site governance. The approach is adaptable to existing supervisory control and data acquisition (SCADA) and SAP Plant Maintenance infrastructures following validation within the site quality system, with early benefit expected when prioritizing product quality critical components such as seals and spray nozzles.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"22-46"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Probabilistic Model to Predict Residual Seal Force of Crimped Vial Seals.","authors":"Dana Cabrita, George Currier, Anthony Petrella, Bereket Yohannes, Jazz Honegger, Ankur Kulshrestha, Srini Sridharan, Yusuf Oni, Elizabeth Moroney","doi":"10.5731/pdajpst.2025-000041.1","DOIUrl":"10.5731/pdajpst.2025-000041.1","url":null,"abstract":"<p><p>One of the most important requirements for a sterile packaging system is container closure integrity (CCI). For vial-based systems composed of a vial, a hyper-elastic stopper, and a rigid crimp seal, CCI testing is an integral part of the drug development process. During the vial-capping process, the component dimensions and materials play a critical role in creating a robust and adequate seal that will satisfy CCI. Although these properties are manufactured within certain tolerances, there exist lot-to-lot variabilities and aging effects. If not taken into consideration during the initial design, these factors can potentially impact the residual seal force (RSF) for a container closure system (CCS). RSF of the vial, while not predictive or causal, is correlated with CCI. For example, it is possible that containers with sufficient RSF can contain defects, including but not limited to fibers, cracks, and folds, that compromise CCI. A robust and efficient deterministic finite element model capable of predicting the RSF for fixed displacement crimping systems was developed for this study. A probabilistic analysis was conducted, and stopper top dimensions (height and outer diameter [OD]) were found to be the most important drivers of seal force magnitude and variation. Seal force was positively correlated with both stopper height and OD. The effect of 2-year accelerated aging of the stopper, prior to assembly, was an increase to material stiffness and corresponding seal force. However, this increase in force was small (∼3%). This corresponds well with practical findings where shelf aging is typically associated with increased material stiffness over time as well as an increase in RSF.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"4-21"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Cleaning Efficacy of Disinfectant Residues on Environmental Surfaces Using a Matrix of Cleaning Solutions and Cleaning Su bstrates: Poster Presented at PDA Microbiology Conference 2025.","authors":"Lauren Pernot","doi":"10.5731/pdajpst.2026.26130","DOIUrl":"https://doi.org/10.5731/pdajpst.2026.26130","url":null,"abstract":"<p><p>The cleaning of process and environmental residues is a crucial aspect of contamination control strategy (CCS) and is mandated by several cGMP regulations. Environmental residues, which remain on surfaces post-disinfection, can accelerate the deterioration of manufacturing area surfaces and pose safety hazards, such as slip and fall risks for operators. The accumulation of environmental residues can also have an impact on the performance of disinfectants and may harbor microorganisms.This study evaluated textiles and rinsing agents and the combined effect they had on the removal of disinfectant residues on various common cleanroom surfaces. Variables included different cleaning solutions and a range of cleaning textiles (mops/wipes) with diverse substrates and textile constructions. The evaluation was conducted quantitatively by incorporating a fluorescent tracer dye into the disinfectant. Pixel analysis measured surface residue after the disinfectant was applied and dried. Subsequently, combinations of cleaning solutions and substrates were used to remove the disinfectant residue, and pixel analysis was performed again to determine the remaining residue.This poster will present the data visually, to provide insight into the considerations that must be made when establishing a residue removal regimen in critical cleanroom spaces.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"80 1","pages":"181-182"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Lonza Built a Digitalized End-To-End Process for Environmental Monitoring: Poster presented at PDA Microbiology Conference 2025.","authors":"Drew Parker, Willem Dullaers","doi":"10.5731/pdajpst.2026.26126","DOIUrl":"https://doi.org/10.5731/pdajpst.2026.26126","url":null,"abstract":"<p><p>Lonza wanted to achieve paperless quality control (QC) laboratories using automated digital systems. As part of this ambition, Lonza sought an end-to-end (E2E) automated solution to optimize environmental monitoring (EM) at four of its Cell & Gene Manufacturing sites across North America, Europe, and Asia. Successful implementation required an innovative approach that harmonized processes across different sites through digital and automation transformation. Lonza successfully integrated the MODA-EM® Module with Rapid Micro Biosystems' Growth Direct® System, combining paperless processes with automated microbial enumeration. This innovative approach is revolutionizing the delivery of critical medicines, accelerating product release, enhancing compliance robustness, and unlocking significant cost savings.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"80 1","pages":"173-174"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"United States Pharmacopeia <73> Microbial Time Detection Assessment: Poster presented at PDA Microbiology Conference 2025.","authors":"Scott Dimond","doi":"10.5731/pdajpst.2026.26111","DOIUrl":"https://doi.org/10.5731/pdajpst.2026.26111","url":null,"abstract":"<p><p>USP < 73> ATP Bioluminescence-Based Microbiological Methods for the Detection of Contamination in Short-Life Products is a new chapter in the USP and becomes effective August 2025. This new rapid method will allow even shorter sterility incubation times based on microbial detection, microorganism generation time(s), applying growth phase curves rationale and utilizing ATP bioluminescence testing.The application of microorganism time studies for medical device and pharmaceutical products will greatly benefit with urgent heath care needs by having data and results available sooner for sterility assurance and critical decision making based upon rapid microbiological methods (RMMs).This poster presentation will focus on experimental data based upon alternative microbiological methods and ATP-bioluminescence results related to microbial detection times, inoculation criteria, generation times and ATP-Bioluminescence technology on various types of microorganism types and testing conditions.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"80 1","pages":"141-142"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147322162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ode to a Sporicide-Can We Do Better?","authors":"Terra Kremer, Donald Singer","doi":"10.5731/pdajpst.2025-000042.1","DOIUrl":"10.5731/pdajpst.2025-000042.1","url":null,"abstract":"","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"71-76"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproducible and Efficient Phenotyping for Cell Therapy Manufacturing Using the Accellix Automated Flow Cytometer Platform.","authors":"Jacob Van Vloten, Seungmi Yoo, Gurleen Sandhu, Leah Teschner, Dinh Nguyen, Rey Mali, Elaine Than, Donna Rill, Chris Ayers, Félix A Montero Julian","doi":"10.5731/pdajpst.2025-000035.1","DOIUrl":"10.5731/pdajpst.2025-000035.1","url":null,"abstract":"<p><p>Measuring cellular quality attributes of cell therapy products is crucial because it ensures their safety, purity, potency, identity, and stability. These attributes help determine whether the therapy is effective and consistent across batches. Since cell therapy products are biologically complex, assessing their quality helps maintain lot-to-lot consistency, supports clinical data generation, and ensures compliance with regulatory standards. Additionally, critical quality attributes are essential for monitoring process control and validating the therapy's effectiveness. Many of these cellular quality attributes are assessed using flow cytometry; however, beyond well-established clinical immunophenotyping assays, the technology remains insufficiently standardized, complicating alignment with Good Manufacturing Practice and regulatory expectations. The work outlined here assesses the feasibility of the Accellix Platform for automated cellular sample analysis by analyzing repeatability and reproducibility across sites, operators, and dedicated instruments. The data presented demonstrate the potential of combining cytometry automation with advanced T cell engineering techniques to achieve robust and compliant manufacturing processes for innovative cellular therapies.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"77-90"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of Limit of In Vitro Cell Age (LIVCA) for Biologics Manufacturing Process.","authors":"Barbara Tevelev, Sharyn Farnsworth, Sarah Kaminsky Pontell, Urška Verbovšek, Guanghua Benson Li, Sean Collins","doi":"10.5731/pdajpst.2025-000013.1","DOIUrl":"10.5731/pdajpst.2025-000013.1","url":null,"abstract":"<p><p>This white paper explores current practices and industry experiences for establishing the Limit of In Vitro Cell Age (LIVCA) in biologics manufacturing. As per the International Council for Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), characterization and testing of banked cell substrate is a critical component of the control of biotechnological and biological products. Regulatory agencies require the establishment of LIVCA for the use of master cell bank (MCB) and working cell banks (WCBs) in commercial manufacturing of biologics to demonstrate that the maximum in vitro cell age of cells used in the production process has no impact on product quality and process consistency over the duration of the cell culture expansion and manufacturing process. This white paper reviews the methodologies for genotypic, phenotypic, and product quality characterization for LIVCA while highlighting the necessity of aligning industry practices with regulatory expectations to expedite market approval. It discusses the strategies for implementing LIVCA, regulatory guidelines, and expectations that shape different industry practices and provides an overview of approval experiences including those based on data derived from production cells expanded under pilot plant scale or using representative scale-down models. Through a collaborative approach involving industry leaders based on an industry-wide survey coordinated by the BioPhorum Operations Group (BioPhorum), we aim to streamline and accelerate LIVCA timelines while ensuring robust manufacturing processes and adherence to high compliance standards as companies design and implement their LIVCA strategies efficiently and effectively to support commercialization applications.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":" ","pages":"104-120"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of MycoSEQ Plus Method for Rapid Mycoplasma Contamination Detection: Poster presented at PDA Microbiology Conference 2025.","authors":"Daniel Berry","doi":"10.5731/pdajpst.2026.26102","DOIUrl":"https://doi.org/10.5731/pdajpst.2026.26102","url":null,"abstract":"<p><p>Testing for mycoplasma contamination in cell banks and bioreactor cell cultures is a regulatory requirement for production of biological products. The compendial tests for mycoplasma detection require 14-28 days incubation, imposing a limitation on batch release timelines and rapid containment in the event of a contamination. The alternative rapid PCR-based mycoplasma detection kit, MycoSEQ Plus, provides results within a few hours and meets regulatory guidelines regarding sensitivity (10 CFU/mL or the genomic equivalent of 10 GC/mL) and specificity as outlined in the European Pharmacopoeia (E.P. 2.6.7, 2007), US Pharmacopoeia (US63), and Japanese Pharmacopoeia. This presentation will discuss the evaluation of the kit's performance by testing its specificity, robustness, and limit of detection.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"80 1","pages":"123-124"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Isolators into Cell, Gene, and Tissue Therapy Manufacturing: Practical Solutions for Challenges Associated with Vaporized Hydrogen Peroxide Decontamination: Poster Presented at PDA Microbiology Conference 2025.","authors":"Zoe Reilly","doi":"10.5731/pdajpst.2026.26135","DOIUrl":"https://doi.org/10.5731/pdajpst.2026.26135","url":null,"abstract":"<p><p>The use of isolators in cell, gene, and tissue therapy manufacturing is increasing due to their support of sterility assurance through effective microbial contamination control. However, many advanced therapy medicinal products (ATMPs) are sensitive to vaporized hydrogen peroxide (VHP), the standard agent used in isolator decontamination. This presents a challenge when transitioning from biosafety cabinets to closed-barrier isolator systems.This poster provides practical solutions to support the integration of isolator technology into ATMP manufacturing while addressing limitations associated with VHP-sensitive materials. Drawing from industry-based experience and collaborative practices, the poster outlines approaches to minimize VHP exposure risks while maintaining contamination control.Topics include isolator design, material selection and placement, process adaptations, and handling strategies for materials both time-sensitive and VHP-sensitive. Operational tips, including techniques to streamline material transfer and reduce open exposure time, are also shared.By offering actionable insights and lessons learned, this presentation aims to help process leads and microbiology professionals better understand how to successfully adopt isolators for ATMP processing. These strategies contribute to building robust, contamination-controlled environments that protect product quality while meeting time-sensitive sterility assurance goals in advanced therapy manufacturing.</p>","PeriodicalId":19986,"journal":{"name":"PDA Journal of Pharmaceutical Science and Technology","volume":"80 1","pages":"191-192"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}